focused on unmet needs in women’s reproductive · medical costs potential to relieve symptoms of...
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Focused on unmet needs in women’s reproductive health
January 2021
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DisclaimerMatters discussed in this presentation may constitute forward-looking statements. The forward-looking statements contained in this presentation reflect our views as of the date of this presentation about future events and are subject to risks, uncertainties, assumptions, and changes in circumstances that may cause our actual results, performance, or achievements to differ significantly from those expressed or implied in any forward-looking statement. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future events, results, performance, or achievements. Some of the key factors that could cause actual results to differ from our expectations include our plans to develop and potentially commercialize our product candidates; our planned clinical trials and preclinical studies for our product candidates; the timing of and our ability to obtain and maintain regulatory approvals for our product candidates; the extent of clinical trials potentially required for our product candidates; the clinical utility and market acceptance of our product candidates; our commercialization, marketing and manufacturing capabilities and strategy; our intellectual property position; and our ability to identify and in-license additional product candidates. For further information regarding these risks, uncertainties and other factors that could cause our actual results to differ from our expectations, you should read he risk factors set forth in our Annual Report on Form 20-F for the year ended December 31, 2019 filed with the SEC on March 5, 2020 and the risk factors disclosed in the Report on Form 6-K filed with the SEC on November 5, 2020, and our other filings we make with the Securities and Exchange Commission from time to time.
We expressly disclaim any obligation to update or revise the information herein, including the forward-looking statements, except as required by law. Please also note that this presentation does not constitute an offer to sell or a solicitation of an offer to buy any securities.
This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. It is currently limited by federal law to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products.
This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.
About ObsEva
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ObsEva (NASDAQ: OBSV and SIX: OBSN) is a clinical-stage biopharmaceutical company developing and commercializing novel therapies to improve women’s reproductive health.Through strategic in-licensing and disciplined drug development, ObsEva has established a late-stage clinical pipeline with development programs focused on treating endometriosis, uterine fibroids and preterm labor
• Founded in 2012
• Locations: Geneva , Switzerland and Boston, MA
• Employees: 46 total EU and US
• Listings: NASDAQ (OBSV) and SIX (OBSN)
• Collaborations with Kissei, YuYuan Bioscience, Merck Serono
Seasoned leadership team
Brian O’CallaghanChief Executive Officer
Elizabeth Garner MD, MPH
Chief Medical Officer
David RenasChief Financial Officer
Fabien de LadonchampsChief
Administrative Officer
Jean-Pierre Gotteland, PhD
Chief Scientific Officer
Wim Souverijns, PhDChief Commercial
Officer
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Board of Directors
Frank Verwiel, MDChairperson
Ernest Loumaye, MD, PhD
Annette Clancy, BSc (Hons)
Barbara DuncanAudit Committee
Chair
James I. Healy, MD, PhD Ed Mathers Rafaèle Tordjman,
MD, PhDJacky Vonderscher,
PhD
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Investor highlights
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Pursuing promising large indications for serious conditions that compromise women's reproductive health and beyond, with the potential to extend into other indications including prostate cancer
Ebopiprant, the only oral PGF2α receptor antagonist in development, has positive phase 2 data and favorable safety that support a Phase 2b dose ranging study (initiation in EU/Asia planned in 2H:21)
Yselty® has potential best in class efficacy, a favorable tolerability profile, and unique flexible dosing options; multiple value-generating milestones in the next year, including:
• Phase 3 uterine fibroids PRIMROSE 76 W data (1Q:21); NDA submission (1H:21); MAA approval for uterine fibroids and regional commercial partnerships pending
• Phase 3 endometriosis EDELWEISS 3 primary endpoint readout (4Q:21)
Strong global partnerships and collaborations support ObsEva approach
Seasoned leadership team with a track record for success to drive meaningful patient data
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2
3
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Product overview
YSELTY®(LINZAGOLIX)
EBOPIPRANT(OBE022)
Potential to delay preterm birth to
improve newborn health and reduce
medical costs
Potential to relieve symptoms of heavy menstrual bleeding due to uterine fibroids and
pain associated with endometriosis
NOLASIBAN
Potential to improve live birth rate
following IVF & embryo transfer
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Multiple development programs drive valuePhase 1 Phase 2 Phase 3 Next Milestones
YSELTY®(LINZAGOLIX)Oral GnRH receptor antagonist
• PRIMROSE 1: 76W data (1Q:21)• NDA submission (2Q:21) • Regional commercial partnerships (1H:21)• MAA for uterine fibroids expected approval
(4Q:21)
• EDELWEISS 3: Primary endpoint readout expected (4Q:21)
EBOPIPRANTOral PGF2αreceptor antagonist
• Initiation Phase 2b dose ranging study in EU and Asia (4Q:21)
NOLASIBANOral oxytocinreceptor antagonist
• Nolasiban Phase 1 in China (1H:21)
Uterine Fibroids – Ph3 PRIMROSE 1 (U.S)
Uterine Fibroids – Ph3 PRIMROSE 2 (EU & U.S)
Endometriosis – Ph3 EDELWEISS 3 EU & U.S.
IVF – Ph1/2 in China
Preterm Labor – Ph2b
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99
EBOPIPRANT
P OTEN TIAL TO D ELAYP RETERM BI RTH TOIMP ROV E N EW BORNH EA LTH A N D RED U CEMED I CA L COSTS
U.S. economic burden$26B /yr >1
In 10 babies are born preterm
preterm related deaths in 2015 WW *
1million
LEADINGcause of deathin childrenunder age 5
Babies surviving early birth face greater likelihood of lifelong disabilities
Preterm birth, a costly burden per baby
$16.9B+ U.S. infant medical costs
$195K+average cost per U.S. survivor infant born 24-26 weeks
$50Kaverage U.S. cost for a preterm infant
WHO ‘Born Too Soon: The Global Action Report on Preterm Birth’ (2012); Kissin et al. NEJM, 2014Behrman et al., National Academies Press, 2007
* WHO: 15 million babies born preterm each year worldwide, and number is rising.
Preterm birth is delivery before 37 weeks of pregnancyLife altering & costly
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Ebopiprant: an advancement in treatment of preterm laborOrally active, selective prostaglandin F2α (PGF2α) receptor antagonist
Potential to treat preterm labor with improved safety over non-selective COX *inhibitors (NSAIDS)
PGE2 PGF2α
PGHS-1/2 =COX1/2
EP1EP3
EP2EP4 FP
PGH2
contractrelaxcontract UTERUS:
Phospholipids
Arachidonic Acid
x
ebopiprantSelectively blocks
the PGF22α
receptor
*COX: cyclooxygenase
Ebopiprant represents an evolution of therapy for preterm labor (PTL)
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• No FDA-approved PTL treatment available in the US*‒ Treatment includes off-label use of COX (non-selective
prostaglandin inhibitors), calcium channel blockers, beta-mimetics‒ Current treatments associated with safety issues that limit use
• Atosiban (intravenous oxytocin receptor antagonist) approved in EU and some Asian countries
• Ebopiprant is an oral selective prostaglandin inhibitor‒ Potential for similar efficacy with improved safety
*Makena is a progestin used for the prevention of PTL in women with a prior history of preterm birth; it is not approved for the treatment of PTL
Ebopiprant is designed to delay delivery by at least 48 hours
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Short-term prolongation of pregnancy (at least 48 hours) provides a critical window for impact on neonatal outcomes:
• Allows full effect of corticosteroids on neonatal lung maturity
‒ Prematurity associated with respiratory complications due to insufficient lung maturation
‒ Corticosteroids used to speed up maturation process‒ Maximum effect occurs ~48+ hours after administration
• Allows patient transfer to centers with NICU*
*NICU=neonatal intensive care unit
Ebopiprant Phase 2a PROLONG study
Hospitalisation
Dosing period and FU visit- Visits at site -
Maternal and neonatal FU- Site visits or medical records -
Infant follow-up- Non-interventional, no site visits -
Term#
+6 MTerm#
+12 MTerm#
+24 Mebopiprant or placebo
Screening and day 1
Follow-up visit
D1 D2 D3 D14
End of treatment
visit
Atosiban
D7
# Expected Term≤24h
Delivery Delivery +28 D
Study design:• Double-blind, randomized• Atosiban + Ebopiprant vs• Atosiban + Placebo
Endpoints:• Incidence of delivery within 48 hours and 7 days of treatment• Time to delivery and delivery prior to 37 weeks of gestation• Maternal, fetal, neonatal safety
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Ebopiprant Phase 2a PROLONG studyDemographics and baseline characteristics
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Atosiban + Placebo Atosiban + Ebopiprantn=55 n=58
Mean age –years (SD) 29.6 (5.1) 29.7 (5.7)
Race
White – n (%) 39 (70.9%) 42 (72.4%)
Asian – n (%) 16 (29.1%) 14 (24.1%)
Mean (SD) gestational age – weeks 29 (3.0) 30.2 (2.6)
24 to 30 weeks – n (%) 23 (41.8%) 25 (43.1%)
30 to 34 weeks – n (%) 32 (58.2%) 33 (56.9%)
Singleton – n (%) 41 (74.5%) 42 (72.4%)
Twin – n (%) 14 (25.5% 16 (27.6%)
Mean (SD) contractions /30 mins 3.19 (2.93) 3.37 (2.97)
Overall delivery rate within 48 hours reduced by > 50%
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Overall GA 24 to 30 weeks
GA 30 to 34 weeks
Singletons Twins0%
10%
20%
30%
n=56
12.5%
n=25
12.0%
n=31
12.9%
n=40
12.5%
n=16
12.5%
n=55
21.8%
n=24
20.8%
n=31
22.6%
n=41
26.8%
n=14
7.1%
Perc
enta
ge o
f sub
ject
s
Placebo + atosiban ebopiprant + atosiban
OR (90% CI) 0.52 (0.22, 1.23) 1.05 (0.20, 5.43) 0.77 (0.21, 2.89) 0.39 (0.15, 1.04) 2.05 (0.23, 18.1)
Percentage of women delivering within 48 hours
Singleton delivery rate within 48 hours reduced by > 50%
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Overall GA 24 to 30 weeks
GA 30 to 34 weeks
0%
10%
20%
30%
40%
n=40
12.5%
n=21
9.5%
n=19
15.8%
n=41
26.8%
n=21
23.8%
n=20
30.0%
Perc
enta
ge o
f sub
ject
s
Placebo + atosiban ebopiprant + atosiban
OR (90% CI) 0.34 (0.08, 1.49)0.39 (0.15, 1.04) 0.44 (0.12, 1.62)
Percentage of women delivering within 48 hours
Singleton 24-30wk delivery rate within 7 days reduced by 40%
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Overall GA 24 to 30 weeks
GA 30 to 34 weeks
0%
10%
20%
30%
40%
50%
n=40
27.5%
n=21
14.3%
n=19
42.1%
n=41
31.7%
n=21
23.8%
n=20
40.0%
Perc
enta
ge o
f sub
ject
s
Placebo + atosiban ebopiprant + atosiban
OR (90% CI) 0.53 (0.14, 2.01)0.81 (0.36, 1.83) 1.09 (0.37, 3.18)
Percentage of women delivering within 7 days
Ebopiprant Phase 2b dose ranging studyAnticipated initiation 2H:21*
Study Design:• Global (EU and Asia) • Dose escalating • Double-blind, randomized• Atosiban + Ebopiprant vs• Atosiban + Placebo
Key Eligibility Criteria:• Single gestation• 24-34 weeks • Confirmed preterm labor• No contraindication to tocolysis
Endpoints:• Optimal dose • Incidence of delivery within 48 hours
and 7 days of treatment• Time to delivery and delivery prior to
37 weeks of gestation• Maternal, fetal, neonatal safety
*Discussions with FDA on requirements for US clinical development to occur in parallel 19
Ebopiprant, a potential breakthrough for preterm labor
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Ebopiprant has demonstrated proof of concept in delaying preterm birth,enabling ObsEva to plan its further development
Enabling administration of critical drugs for neonatal
protection
Maternal, fetal and neonatal safety
comparable to placebo
Over 50%reduction of
premature deliverywithin 48 hrs
Supportsadvancingebopiprant
into Phase 2b
Phase 2b study will include higher
doses to more fully define ebopiprant potential and the longer-
term benefits for babies
Favorablematernal,fetal and
neonatal safety
D ES IG NED TO TREAT MOREWOMEN S U F F ERIN G F ROMU TERIN E F IBROID S
Yselty®, our proposed trade name for linzagolix, is conditionally acceptable for the FDA. Linzagolix has not been approved by FDA for any indication for use. Linzagolix is an investigational drug.
Uterine fibroids A significant unmet need translating into a multibillion market
total U.S. costs from direct costs, lost workdays and complications
$34B /yr 9millionwomen in the U.S.affected by fibroids
of women have fibroids by age 50
70%+
Quality of Life
600,000
300,000
>4 million
premenopausal women may experience heavy menstrual bleeding, anemia, bloating, infertility, pain and swelling
hysterectomies are performed annually in the U.S.
women in the U.S. are treated annually for fibroids
are because of uterine fibroids
22Cardozo et al., Am J Obstet Gynecol 2012; Stewart et al. NEJM, 2015; Flynn et al., Am J Obstet Gynecol 2006; Truven Health, Fibroid Foundation website; Epidemiology of women’s health, Jones & Bartlett Learning, Ruby T. Senie, 2014
GnRH antagonist mechanism of action
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1. Yselty® binds competitively to pituitary glandGnRH receptors
2. Prevents receptor activation by endogenous GnRH
3. Rapid suppression of LH and FSH
4. Gonadotropin suppression leads to dose-dependent decrease in serum estradiol concentration
Hypothalamus
Anterior pituitary gland
FSH, LH
EstradiolOvary
GnRH
Yselty® (linzagolix)
Uterus
Yselty® is the only GnRH antagonist being developed to provide differentiated options for women suffering from uterine fibroids
The promise of the GnRH antagonistsDose dependent reduction of estradiol (E2)
24
60
20
E2 c
once
ntra
tion
(pg/
mL)
1
OptimalRange
2Partial suppression reduces E2 into the optimal zone, minimizing BMD loss and eliminating the need for
ABT
Full suppression virtually eliminates E2, requiring ABT to return to the
optimal zone and minimizing BMD loss
+ ABT
Symptoms
BMD loss0
ABT = Add Back Therapy (1mg estradiol + 0.5 mg norethindrone acetate)BMD = Bone Mineral Density
100
200 mg with ABT 100 mg without ABT
Bioavailability> 80%
Half-life14-15 hours
No CYP3A4induction/food
effect
A potential new gold standard treatment for uterine fibroidsDifferentiated PK/PD profile
25
Reliable absorptionPredictable exposure/effect with each dose
1
Optimal balance for dosing and effectiveness• Convenient once-daily
dosing that fits into women’s busy lives
• Blood levels that last long enough to allow flexibility in dosing time
2
“No hassle” administration profile• Can be taken with or
without food• No relevant interactions
with hormonal add-back therapy, oral iron, calcium or other common medications
3
Uterine fibroids are ruining lives…
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No two women are the same, but millions share a common problem: suffering the daily consequences of uterine fibroids
…Yselty®, designed to treat more women
Yselty® 200 mg once daily without ABT
Yselty® 100 mg once daily without ABT
Yselty® 200 mg once daily with concomitant ABT
For short-term use (up to 6 months) when rapid reduction in fibroid and
uterine volume is desired
For long-term use for women with a contraindication to or who prefer
to avoid ABT
For long-term use for women for whom ABT is appropriate
The hypothetical patients represented on this slide are for illustrative purposes only as no strength of linzagolix has been approved nor is there FDA-approved Prescribing Information to guide clinical decisions
Up to 50% of US women suffering from uterinefibroids may have a contraindication to hormonal ABT*Black women are overrepresented
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0%
10%
20%
30%
40%
50%
60%
Obesity (BMI ≥ 30)in womenaged ≥20
Non-Hispanic Black
Non-hispanic White
Severe obesity(BMI ≥40) inwomen aged
≥20
Smokers aged ≥18 Hypertensionuncontrolled**
Dyslipidemia Genetic risk factorsfor Venous
thromboembolism
Prop
ortio
n of
U.S
. pop
ulat
ion
(%)
Proportion of U.S. population
https://www.cdc.gov/nchs/products/databriefs/db360.htm: 2017-2018; https://www.cdc.gov/nchs/products/databriefs/db360.htm: 2017-2018; https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm#nation; https://www.cdc.gov/2018
** Proportion of individuals with hypertension - Overall population Male vs Female: 47% vs 43%
*U.S. FDA elagolix PI, section 4. Contraindications and section 5.1. Warnings and precautions – thromboembolic disorders and vascular events (see slide 26) ** See slide 27
28ABT = Add Back Therapy (1mg estradiol + 0.5 mg norethindrone acetate)
Primary efficacy endpoint is proportion of women with menstrual blood loss ≤ 80 mL (by alkaline hematin method) and ≥ 50% reduction from baseline
2 full menstrual cycles 24 weeks 28 weeks 24 weeks
n = 103/102
n = 94/97
n = 107/101
n = 105/103
n = 102/98
100 mg + ABT
200 mg + ABT
24-WeekPost Treatment
Follow-up
Double-Blind Treatment Double-Blind Treatment
Placebo 200 mg + ABT
100 mg 100 mg
100 mg + ABT
200 mg + ABT
Primary efficacy endpointKey secondary endpoints, Safety
P1/P2
Screening
Phase 3 registration studiesPRIMROSE 1 (US) and PRIMROSE 2 (EU/US)
Patients in the studies received no Vitamin D or calcium supplementation
Placebo (P1 only)
200 mg 200 mg + ABT
Placebo Linzagolix100 mg
Linzagolix200 mg + ABT
Placebo Linzagolix100 mg
Linzagolix200 mg + ABT
Placebo Linzagolix100 mg
Linzagolix200 mg + ABT
0%
20%
40%
60%
80%
100%
75.5%
93.9%84.5%
56.4% 56.7% 56.5%
35.0%29.4% 32.2%
Prop
ortio
n of
wom
en
PRIMROSE 1Week 24
PRIMROSE 2Week 24
PRIMROSE 1 and 2Week 24 pooled
PRIMROSE 1 and 2 achieved primary endpoint for both doses Responder* analysis at week 24
29*Proportion of women with menstrual blood loss ≤ 80 mL (by alkaline hematin method) and ≥ 50% reduction from baselineError bars are 95% CI
P=0.003
P<0.001
P<0.001
P<0.001
n=103 n=94 n=102 n=102 n=97 n=98 n=205 n=191 n=200
P<0.001
P<0.001
Placebo Linzagolix100 mg
Linzagolix200 mg + ABT
Linzagolix100 mg
Linzagolix200 mg + ABT
Linzagolix100 mg
Linzagolix200 mg + ABT
0%
20%
40%
60%
80%
100%
n=66
86.4%
n=83
91.6%
n=149
89.3%
n=61
60.7%
n=79
53.2%
n=140
56.4%
n=31
38.7%
Prop
ortio
n of
wom
en
PRIMROSE 1Week 52
PRIMROSE 2Week 52
PRIMROSE 1 and 2Week 52 pooled
PRIMROSE 1 and 2 achieved sustained reduction in MBL Responder* analysis at week 52
30*Proportion of women with menstrual blood loss ≤ 80 mL (by alkaline hematin method) and ≥ 50% reduction from baseline
Significant pain reduction maintained at weeks 52 and 64
31
P1 Wk 24 P1 Wk 52 Week 24 Week 52 Week 64
-5
-4
-3
-2
-1
0 n=65
-3.7
n=44
-3.9
n=80
-2.1
n=73
-2.8
n=54
-1.2
n=62
-2.8
n=47
-3.3
n=76
-2.2
n=55
-2.6
n=49
-1.9
n=63-0.6
n=21 n=83
-0.7
Mea
n ch
ange
from
base
line
in p
ain
scor
e
PlaceboLGX 100 mgLGX 200 mg + ABT
Error bars are 95% CI
PRIMROSE 1 PRIMROSE 2
Pain assessed on Numerical Rating Scale: 0-10
LGX 200 mg without ABT significantly reduces uterine volumeSubstantial reduction compared to placebo & LGX 200 mg with ABT at Week 24
32
-200
-100
0
100
PRIMROSE 2
Weeks
12 24 36Baseline 52
Error bars are 95% CI
Placebo LGX 200 mg/200 mg + ABTLGX 200 mg + ABT
-200
-100
0
100
PRIMROSE 1
Weeks
Mea
n C
FBut
erin
e vo
lum
e cm
3
12 24 36Baseline 52
24-week efficacy data support Yselty® (linzagolix) as potential best-in-class GnRH antagonist
Source: Company information Note: NR = Not reported.*Primary endpoint: Proportion of women with menstrual blood loss ≤ 80 mL (by alkaline hematin method) and ≥ 50% reduction from baseline ** P-value not reported
+ Simon et al, Obstet Gynecol 135, 1313-1326 2020 ++ Venturella R et al, ESHRE 2020 abstract.
Yselty® (Linzagolix) Elagolix Relugolix
PRIMROSE 1 PRIMROSE 2 Pooled Analysis ELARIS 1 ELARIS 2 Pooled
Analysis LIBERTY 1 LIBERTY 2 Pooled Analysis
Dose Regimen 200mg + ABTOnce daily
300 mg + ABTTwice daily
40mg + ABTOnce daily
Mean Age (y) 41.6 43.1 42.6 42.5 41.3 42.1
Baseline MBL (mL per cycle) 197 212 238 229 229 247
Responder* Rate (RR) (%) 75.5 93.9 84.7 68.5 76.5 72.2+ 73.4 71.2 72.3++
AmenorrheaPainFibroid VolumeUterine VolumeMenstrual Blood LossAnemiaQuality of Life
NRNR**
NR**
NR NR**
NR**
Caution advised when comparing across clinical trials. Below data are not head-to-head comparison, and no head-to-head trials have been completed, nor are underway
3333
Minimal BMD change with both doses, plateauing after week 24Expected age-related BMD decline observed in placebo arm at Week 52
34
Week 24 Week 52
-10%
-8%
-6%
-4%
-2%
0%
2%
-1.4%
n=72-2.0%
n=60
-2.1%
n=71
-2.4%
n=55
n=78
PRIMROSE 2
Error bars are 95% CI
0.5%
Week 24 Week 52
-10%
-8%
-6%
-4%
-2%
0%
2%
-0.8%
n=56
-1.3%
n=38
-2.0%
n=50-3.6%
n=40
n=52
-2.3%
n=20
PRIMROSE 1
Mea
n %
cha
nge
from
bas
elin
elu
mba
r spi
ne B
MD
PlaceboLinzagolix 100 mgLinzagolix 200 mg + ABT
0.4%
Recovery at 6 months post-treatment (in subjects with a decrease at Week 52): Median % BMD increase: LGX 100 mg about 0.8%, LGX 200 mg + ABT about 1.2%
Bone mineral density – no change in z-scoresBMD remains well within age-matched normal ranges during and after treatment for both doses
35
Baseli
ne
Week 2
4
Week 5
2-4
-2
0
2
4
6P1 Placebo
z-sc
ore
Baseli
ne
Week 2
4
Week 5
2-4
-2
0
2
4
6P1 LGX 100 mg
z-sc
ore
Baseli
ne
Week 2
4
Week 5
2-4
-2
0
2
4
6P1 LGX 200 mg + ABT
z-sc
ore
Baseli
ne
Week 2
4-4
-2
0
2
4
6P2 Placebo
z-sc
ore
Baseli
ne
Week 2
4
Week 5
2
Week 7
6-4
-2
0
2
4
6P2 LGX 100 mg
z-sc
ore
Baseli
ne
Week 2
4
Week 5
2
Week 7
6-4
-2
0
2
4
6P2 LGX 200 mg + ABT
z-sc
ore
Z-score compares BMD to the average values of a person of the same age and gender. A score < -2 is a sign of less bone mass than expected
Favorable tolerability profileSummary of adverse events—week 24 to 52
36
Number (%) of women
PRIMROSE 1 PRIMROSE 2
PlaceboYselty®
(Linzagolix)100 mg
Yselty® (Linzagolix)
200 mg + ABT
Yselty® (Linzagolix)100 mg
Yselty® (Linzagolix)200 mg + ABT
n=31 n=62 n=70 n=79 n=84
Subject with at least one TEAE 12 (38.7) 25 (40.3) 25 (35.7) 22 (27.8) 21 (25.0)
TEAE leading to discontinuation 1 (3.2) 2 (3.2) 1 (1.4) 7 (8.9) 1 (1.2)
SAE related to linzagolix 0 0 0 0 0
Occurrence after week 24 of most frequently reported AEs (> 5%) up to week 24
Hot flush 0 1 (1.6) 0 2 (2.5) 3 (3.6)
Headache 1 (3.2) 3 (4.8) 0 1 (1.3) 1 (1.2)
Anemia 1 (3.2) 0 0 2 (2.5) 1 (1.2)
No signal related to adverse events of interest*Adverse events of interest/pregnancy – week 24 to 52
37
Number (%) of women
PRIMROSE 1 PRIMROSE 2
Placebo Yselty® (Linzagolix)100 mg
Yselty® (Linzagolix)200 mg + ABT
Yselty® (Linzagolix)100 mg
Yselty® (Linzagolix)200 mg + ABT
n=31 n=62 n=70 n=79 n=84
Suicidal ideation 0 0 0 0 0
Depression; depressed mood 0 0 0 0 0
Anxiety 0 0 0 0 0
Alopecia 0 0 0 0 1 (1.2)
Decreased libido 0 0 0 0 1 (1.2)
Pregnancy 0 0 0 1 (1.3) 0
* Adverse events of interest are AEs that are potentially related to suppression of estradiol and have been reported with Oriahnn treatment
ABT-containing regimens may be contraindicated in up to 50% of US womenwith uterine fibroids based on the elagolix US label* and analysis of CDC data**
38
Potentially best-in-class
Favorabletolerability
profile
Unique setof treatment
options
*U.S. FDA elagolix PI, section 4. Contraindications and section 5.1. Warnings and precautions – thromboembolic disorders and vascular events (see slide 26)** See slide 27
Designed to treat more womenExcellent clinical data driving differentiated profile
• No safety signal of concern for any of the Yselty® regimens
• BMD remains within age-matched normal ranges during and after treatment
• Unique PD/PK Profile • Efficacy sustained up to 52 weeks for
all dose regimens• Potentially best-in-class symptom
control for 200 mg with ABT
• Unique low dose option without ABT showing clinically meaningful & sustained efficacy
• Significant uterine volume reduction for 200 mg without ABT
EndometriosisAn emotionally and physically painful condition
total U.S. costs$22B /yr 176million
women worldwidesuffer from endometriosis
of women feel symptoms byage 16
60%+
Quality of Life
5million
premenopausal women may experience pelvic pain, pain during intercourse and defecation, infertility and emotional distress
Endometriosis affects up to
women in the U.S. are treated annually for endometriosis
39Cardozo et al., Am J Obstet Gynecol 2012; 2017; Stewart et al. NEJM, 2015; Flynn et al., Am J Obstet Gynecol 2006;Truven Health, Fibroid Foundation website
10%+in the general population
50%+in the fertile population
60%+in patients with chronic pelvic pain
40* Titration after 12 weeks based on E2 serum level at weeks 4 and 8**BMD = bone mineral density
8-14 weeks 24 weeks 24 weeks
75 mg daily
100 mg daily
200 mg daily
Placebo
50 mg daily 50 mg daily
50 mg daily
100 mg daily
200 mg daily
Primary efficacy endpoint: VRS PAIN SCORE RESPONDER RATESecondary endpoint: BMD**
Lead-in
Phase 2b EDELWEISS in endometriosis
75 mg daily* Titrated dose 50-100 mg
Optional extension:6M + 6Mfollow-up
Enrollment 328 patients, ~65/arm 50 sites in U.S. (n=177)14 sites in EU (n= 151)
Follow-up
Patients were provided with Vitamin D and calcium
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Phase 2b EDELWEISS in endometriosis
Overall Pelvic Pain (%)
34,5
61,570,8
56,3
77,3
Week 12 Week 24
Plc 75mg 200mg
***
Potential point of differentiation as 75mg partial suppression dose is nearly as effective as 200mg full suppression dose
* p value <0.05 ** p value <0.01 *** p value <0.001 for linzagolix doses compared to placebo
28,5
0
68,258,3
78,9 84,1
Week 12 Week 24
Plc 75mg 200mg
Dysmenorrhea (%)
Non-menstrual Pelvic Pain (%)
Responder (0-3 VRS)
Responder (0-3 VRS)
37,1
58,572,9
47,7
72,7
Week 12 Week 24
Plc 75mg 200mg
*** ***
*
Responder (0-3 VRS)
42
Phase 2b EDELWEISS in endometriosisSustained improvement in overall endometriosis symptoms (PGIC)
PGIC (%)% Much and very much improvement (%)
26.8
48.9*
61.7 64.355.8 *
7076.2
Plc 75 mg 200 mg
Week 12 Week 24 Week 52
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Phase 2b EDELWEISS in endometriosis75 mg effective without significantly affecting BMD
-4
-3
-2
-1
0
1
2
Lumbar Spine Total hip Femoral neck
200mg
100mg
75mg FD
50mg
Placebo
Mean % change in BMD from baseline to 24 weeks (12 weeks for placebo)
75mg 200mg
Error bars are 95% CIs
44ABT: Add Back Therapy (estradiol + norethindrone acetate)
11±5 weeks 24 weeks
75 mg daily
200 mg daily + ABT
Placebo 200 mg daily + ABT
75 mg daily
200 mg daily + ABT
Co-Primary efficacy endpoint: DYS/NMPP Responder Analysis
Lead-in
Phase 3 endometriosis trialEDELWEISS 3
24 weeks treatment 24 weeks extension
75 mg daily
Post TreatmentFollow-up
Patients are provided with Vitamin D and calcium
Investor highlights
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Pursuing promising large indications for serious conditions that compromise women's reproductive health and beyond, with the potential to extend into other indications including prostate cancer
Ebopiprant, the only oral PGF2α receptor antagonist in development, has positive phase 2 data and favorable safety that support a Phase 2b dose ranging study (initiation in EU/Asia planned in 2H:21)
Yselty® has potential best in class efficacy, a favorable tolerability profile, and unique flexible dosing options; multiple value-generating milestones in the next year, including:
• Phase 3 uterine fibroids PRIMROSE 76 W data (1Q:21); NDA submission (1H:21); MAA approval for uterine fibroids and regional commercial partnerships pending
• Phase 3 endometriosis EDELWEISS 3 primary endpoint readout (4Q:21)
Strong global partnerships and collaborations support ObsEva approach
Seasoned leadership team with a track record for success to drive meaningful patient data
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Thank you